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Small Endogenous Ligands Modulation of Nerve Growth Factor Bioactivity: A Structural Biology Overview.
- Source :
-
Cells [Cells] 2021 Dec 08; Vol. 10 (12). Date of Electronic Publication: 2021 Dec 08. - Publication Year :
- 2021
-
Abstract
- Experiments with cell cultures and animal models have provided solid support for the assumption that Nerve Growth Factor (NGF) plays a key role in the regulation of neuronal cell survival and death. Recently, endogenous ligands have been proposed as physiological modulators of NGF biological activity as part of this regulatory cascade. However, the structural and mechanistic determinants for NGF bioactivity remain to be elucidated. We recently unveiled, by an integrated structural biology approach, the ATP binding sites of NGF and investigated the effects on TrkA and p75 <superscript>NTR</superscript> receptors binding. These results pinpoint ATP as a genuine endogenous modulator of NGF signaling, paving the way to the characterization of not-yet-identified chemical diverse endogenous biological active small molecules as novel modulators of NGF. The present review aims at providing an overview of the currently available 3D structures of NGF in complex with different small endogenous ligands, featuring the molecular footprints of the small molecules binding. This knowledge is essential for further understanding the functional role of small endogenous ligands in the modulation of neurotrophins signaling in physiological and pathological conditions and for better exploiting the therapeutic potentialities of NGF.
- Subjects :
- Animals
Binding Sites genetics
Humans
Ligands
Nerve Growth Factor chemistry
Nerve Growth Factor genetics
Nerve Growth Factors genetics
Neurons metabolism
Neurons ultrastructure
PC12 Cells
Protein Binding genetics
Rats
Signal Transduction genetics
Nerve Growth Factor ultrastructure
Nerve Growth Factors ultrastructure
Receptor, Nerve Growth Factor genetics
Receptor, trkA genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4409
- Volume :
- 10
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- 34943971
- Full Text :
- https://doi.org/10.3390/cells10123462